KIAA0319-like protein (AAVR) (AAVR)

KIAA0319-like protein, also known as the Adeno-associated virus receptor (AAVR), is a type I transmembrane protein that serves as the primary cell-surface entry receptor for various adeno-associated virus (AAV) serotypes, including the AAVHSC15 variant. AAVHSC15 belongs to a clade of AAVs (Clade F) isolated from human hematopoietic stem cells, which are utilized in gene therapy for their ability to cross the blood-brain barrier and target the central nervous system. The receptor contains five polycystic kidney disease (PKD) domains, and AAVHSC15 specifically interacts with the second domain (PKD2) to initiate infection. Upon binding, the receptor facilitates the internalization of the viral capsid through endocytosis and guides its trafficking through the trans-Golgi network toward the nucleus. While AAVHSC15 was initially noted for its distinct tropism, its dependence on AAVR for cellular entry has been confirmed, making AAVR a critical factor in the development and efficacy of AAVHSC-based therapeutic vectors. Understanding the expression patterns and binding kinetics of AAVR is vital for optimizing the delivery of gene-editing and gene-replacement therapies using AAVHSC15.

Other names

KIAA0319LAdeno-associated virus receptorAAV receptorAAVHSC entry receptor

The AAVHSC15 capsid binds to the PKD2 domain of the KIAA0319-like protein (AAVR) on the cell surface, which facilitates the internalization of the viral vector via receptor-mediated endocytosis and its subsequent trafficking to the nucleus for gene expression.